This shared instrumentation proposal from the structural biology program at the Fred Hutchinson Cancer Research Center requests funding for the acquisition of high-performance, graded multilayer X-ray optics. These will update and maximize the capabilities of an existing macromolecular crystallographic data-collection system employed by five principal investigators and their laboratories. The upgrade of this integrated instrument system will greatly facilitate ongoing collaborative efforts both within the center and with a large number of molecular biology and biochemistry laboratories throughout the country. The macromolecular structure program at the Hutchinson Center was established approximately seven years ago as a response to a clear need among the molecular biology laboratories at the Center for collaborative structure/function studies which support their research programs in genetic regulation, developmental biology, signal transduction, cell cycle control, and other basic biological phenomena. In addition, all five principal investigators listed below actively conduct their own original research in such areas as structural enzymology, time-resolved crystallography, viral protein structure, protein-nucleic acid recognition, RNA structure, immune system recognition and response, protein engineering, crystallographic phasing, and protein folding. It is thus necessary to maximize the capabilities of our X-ray equipment to satisfy our requirements for efficient and accurate data collection. The goal of this proposal is to update cost-effectively our shared diffraction facility by replacing suboptimal graphite monochromator and Franks-type mirrors with state-of-the-art graded multilayer X-ray optics. We are requesting funds to purchase MSC/Max-Flux confocal optics that will result in up to 27-fold increase in useable X-ray flux, relative to the current configuration.